1. Field of the Invention
The present invention relates to psychiatric and neuropsychiatric disorders, such as schizophrenia, schizoaffective disorder, bipolar disorder, and Alzheimer's disease and, more particularly, to the role of GTP cyclohydrolase I gene, GTP cyclohydrolase (GTPCH), biopterins, and tetrahydrobiopterin in the detection, diagnosis, prognosis and treatment of such disorders.
2. Description of the Related Art
Schizophrenia (SZ) and schizoaffective disorder (SaD) are among the most common forms of mental illness, and have large genetic and heritable components, indicated by studies showing increased risk among first degree relatives, and concordance between mono- and dizygotic twins. The genetic components of SZ and SaD appear to involve multiple genes. Individuals with these psychiatric disorders can display an overlapping range of symptoms and there appears to be increased prevalence of SZ in the families of SaD sufferers, and vice versa. There have also been reports of shared genetic susceptibility loci for these disorders.
Tetrahydrobiopterin (BH4) is a vital cofactor maintaining availability of the amine neurotransmitters, dopamine (DA), noradrenaline (NA), and serotonin (5-HT). BH4 is also involved in regulating the synthesis of nitric oxide (NO) by nitric oxide synthases (NOS), and stimulating and modulating the glutamatergic system. In the central nervous system (CNS), BH4 has also been shown to stimulate the release of DA, 5-HT and glutamate, as well as regulating the expression of tyrosine hydroxylase at nerve terminals. Plasma total biopterins level (biopterin) is a measure of BH4 (approximately 80-90% in the form of BH4) and are correlated with CNS biopterin levels.
Conventional methods do not rely on a genetically based method for assessing the presence or risk of schizophrenia or schizoaffective disorder using the GTP cyclohydrolase I (GCH1) gene alone or in conjunction with a biochemical assay. These method also fail to disclose a method of treating psychiatric and neuropsychiatric diseases, such as schizophrenia, by addressing genetic deficiencies in the GCH1 gene and/or in the BH4 system. For example, there is currently no useful genetic test for determining subjects that are at-risk for developing schizophrenia and, as a result, treatment approaches have limited success.